• Helga Radner, Sofia Ramiro, Rachelle Buchbinder, Robert B M Landewé, Désirée van der Heijde, and Daniel Aletaha.
• Division of Rheumatology,Department of InternalMedicine 3,MedicalUniversityVienna,Vienna, Austria.helga.radner@meduniwien.ac.at.
• Cochrane Db Syst Rev. 2012 Jan 18; 1 (1): CD008951CD008951.

BackgroundEven with optimal disease-modifying treatment and good control of disease activity, persistent pain due to structural damage is common in people with inflammatory arthritis and therefore additional treatment for pain might be required. Because comorbidity is highly prevalent in people with inflammatory arthritis, it is important to consider comorbidities such as gastrointestinal or liver diseases in deciding upon optimal pharmacologic pain therapy.ObjectivesTo assess the efficacy and safety of pharmacological pain treatment in patients with inflammatory arthritis who have gastrointestinal or liver comorbidities, or both.Search MethodsWe searched MEDLINE, EMBASE and Cochrane CENTRAL for studies to June 2010. We also searched the 2007-2010 ACR and EULAR abstracts and performed a hand search of reference lists of articles.Selection CriteriaAll randomised or quasi-randomised controlled trials (RCTs or CCTs) were considered for inclusion for assessment of efficacy. For safety we also considered single arm trials, controlled before-after studies, interrupted time series, cohort and case-control studies, and case series of 10 or more consecutive cases. Pain therapy comprised paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, opioid-like drugs (tramadol) and neuromodulators (anti-depressants, anticonvulsants and muscle relaxants). The study population comprised adults (>18 years) with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or other spondyloarthritis who had gastrointestinal and/or hepatic comorbid conditions. Outcomes of interest were pain, adverse effects, function and quality of life. Studies that included a mixed population of inflammatory arthritis and other conditions were included only if results for inflammatory arthritis were reported separately.Data Collection And AnalysisTwo review authors independently selected trials for inclusion, assessed risk of bias and extracted data.Main ResultsOut of 2869 articles only one single arm open trial was identified that fulfilled our inclusion criteria. This trial assessed the safety and efficacy of naproxen (dosage not specified) in 58 patients with active rheumatoid arthritis and gastrointestinal comorbidities for up to 52 weeks. Thirteen participants (22%) remained on gold therapy, four participants (10%) remained on hydroxychloroquine, 27 (47%) remained on corticosteroids, 12 (21%) remained on salicylates and all participants continued on antacids and bland diet. The presence of faecal occult blood was reported in 1/58 participants tested between weeks 1 to 26 and 2/32 participants tested between weeks 27 to 52. Over the course of the study, seven participants (12.1%) withdrew due to adverse events but of these, only two participants withdrew due to gastrointestinal side effects (abdominal pain n=1, nausea n=1) and no serious adverse events were reported. Noteable, out of 14 studies excluded due to inclusion of mixed population (osteoarthritis or other rheumatic conditions) or intervention already withdrawn, five trials reported higher risk of developing gastrointestinal events in patients with prior gastrointestinal events when treated with NSAIDs.Authors' ConclusionsOn the basis of the current review, there is scant evidence to guide clinicians about how gastrointestinal or liver comorbidities should influence the choice of pain treatment in patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or other spondylarthritis. Based upon additional studies that included a mixed population of participants with a range of rheumatic conditions, NSAIDs should be used cautiously in patients with inflammatory arthritis and a history of gastrointestinaI comorbidity as there is consistent evidence that they may be at increased risk.

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